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Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for cancer therapy. In this study we describe for the first time the use of dynamic boolean modeling for tumor growth prediction of vaccinia virus GLV-1h68-injected canine tumors including canine mammary adenoma (ZMTH3), canine mammary carcinoma (MTH52c), canine prostate carcinoma (CT1258), and canine soft tissue sarcoma (STSA-1). Additionally, the STSA-1 xenografted mice were injected with either LIVP 1.1.1 or LIVP 5.1.1 vaccinia virus strains. Antigen profiling data of the four different vaccinia virus-injected canine tumors were obtained, analyzed and used to calculate differences in the tumor growth signaling network by type and tumor type. Our model combines networks for apoptosis, MAPK, p53, WNT, Hedgehog, TK cell, Interferon, and Interleukin signaling networks. The in silico findings conform with in vivo findings of tumor growth. Boolean modeling describes tumor growth and remission semi-quantitatively with a good fit to the data obtained for all cancer type variants. At the same time it monitors all signaling activities as a basis for treatment planning according to antigen levels. Mitigation and elimination of VACV- susceptible tumor types as well as effects on the non-susceptible type CT1258 are predicted correctly. Thus the combination of Antigen profiling and semi-quantitative modeling optimizes the therapy already before its start.

Specific colonization of solid tumors by bacteria opens the way to novel approaches in both tumor diagnosis and therapy. However, even non-pathogenic bacteria induce responses by the immune system, which could be devastating for a tumor bearing patient. As such effects are caused e.g., by the lipid A moiety of the lipopolysaccharide, a msbB-mutant of the probiotic E. coli Nissle 1917 strain was investigated. Bacteria of the mutant strain did not show any growth defects in culture media when compared to wild-type E. coli Nissle 1917 but were unable to myristoylate lipid A, had less toxic effects on immunocompetent BALB/c mice, and were still able to specifically colonize tumors. Therefore, the modification of lipid A could result in bacterial strains that might be better suited for diagnosis and therapy of tumors than the corresponding wild-type strains, even if those are not considered pathogenic or are of probiotic background.